Pre- Drug Use % of Treated Patients on Medication 60 50 40 30 20 10 0 1978 Diuretics ß-Blockers ACE Inhibitors Year CCBs CCBs Beta Blockers Diuretics ACE Inhibitors 1980 1982 1984 1986 1988 1990 1992 IMS Health NDTI, 1978-1992 1992
Background In addition to their BP lowering potential all antihypertensive agents have other important mechanisms of action, indications, and side effects. These actions may convey benefits or risks independent of BP lowering By having a common BP goal for all treatment arms, aimed to evaluate the health effects of these non-bp actions
Overall Purpose To determine whether the newer, more costly antihypertensive drugs - CCBs, ACE inhibitors and alpha-blockers - are superior to the older, less expensive diuretics in preventing CV complications of hypertension.
Health Effects of Diuretics Low-dose thiazide-type type diuretic-based treatment in large clinical trials has been shown to reduce the risks of: Event reduction % Stroke 34 Heart failure 42 CHD 28 CVD mortality 24 Total mortality 10 Psaty et al., JAMA 1997;277:739-45
Strengths Largest hypertension trial ever (n=42,418); practice-based Diverse study population High methodologic standards Independent sponsorship and conduct Conclusions based on 10,834 cardiovascular events
Implications 1. Selection of first-line drug 2. Selecting treatments for particular patients 3. Drug cost and health benefit To patients To society 4. Design of future hypertension trials 5. Impact on treatment guidelines
Selection of 1 st -line Drug - Conclusions Among antihypertensive drugs, thiazide- like diuretics were unsurpassed in: long-term drug adherence controlling elevated blood pressure and were superior to other therapies in preventing one or more forms of cardiovascular events having lower drug cost
Selection of 2 nd -line Drug(s) - Type of Add-on Large proportion of hypertensive patients require additional drug(s) for BP control No direct comparison of 2 nd -line drugs in Optimal type of add-on agent unknown Need for large trials comparing different classes of agents added to diuretics
2002 Use of Antihypertensive Medications, Proportion of Drug-Treated Patients by Drug Class 40% 37% 30% 27% % Patients 20% 10% 20% 20% 19% 0% Source: NDTI -- IMS HEALTH Calcium Channel Blockers Diuretics ACE- Inhibitors Beta- Blockers ARBs
Selecting Treatments for Particular Patients I Benefits of diuretics generalizable to: Men and women Age group <65 and > 65 yrs Blacks and non-blacks Diabetics and non-diabetics Presence and absence of other co- morbidity
Selecting Treatments for Particular Patients II Diuretics are better than: - ACEIs (lisinopril) for patients at high risk of CVD events, especially heart failure, as well as for African-Americans Americans at risk of stroke - Alpha-blockers (doxazosin( doxazosin) ) for patients at high risk of heart failure, stroke, angina and coronary revascularizations - CCBs (amlodipine) for patients at high risk of developing heart failure
Selecting Treatments for Patients - Conclusions Thiazide-type diuretics should be considered for nearly all patients with hypertension: Untreated patients Inadequately controlled patients on non-diuretic agent(s) Controlled patients on non-diuretic agent(s) unless compelling indication exists for another agent
Drug Cost to Patient (U.S. 2002) Annual Chlorthalidone $ 36 Amlodipine $679 Lisinopril - branded $533 - generic** $280 *Drugstore.com (exclusive of dispensing fee) **available 3 rd quarter 2002
Drug Cost to Society Average Annual Drug Cost/Pt* No. of Annual Users** Total Drug Cost** ACEIs $280-12.7 $3,556-533 6,769 CCBs $679 9.3 $6,315 Diuretics $ 36 6.9 $ 248 *price of largest selling drug/class (2002) **in million
Excess CV Events 6-yr Total Excess Excess Users* events/yr** ACEIs Comb CV 2.3% 12.7 48,700 Events CCBs CHF 2.5% 9.3 38,800 *in million **concomitant use of diuretics may reduce these numbers by up to 20%
Design of Hypertension Trials Thiazide-like diuretics, in low to moderate dose, should be the treatment control group of future comparative trials in patients with hypertension.
Treatment Guidelines Thiazide-like diuretics, in low to moderate dose, should be the guideline-recommended first-line drug treatment for nearly all patients with hypertension.
Conclusions I The benefit of diuretics as first-line therapy applies to nearly all patients with hypertension Diuretics are superior or unsurpassed in reducing the risks of cardiovascular complications Diuretics are the least expensive agents for treating hypertension
Conclusions II Translating the findings into practice will reduce the financial cost of antihypertensive drugs and reduce the societal burden of CV complications Future comparative hypertension trials should use diuretics as the control group or base therapy Treatment guidelines are being revised to reflect the findings